Zhu Zhigang, Kaiser Thomas, Staley Christopher
Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
BioTechnology Institute, University of Minnesota, St. Paul, MN, USA.
Methods Mol Biol. 2021;2327:281-291. doi: 10.1007/978-1-0716-1518-8_17.
Mice transplanted with human microbiota are essential tools for studying the role of microbiota in health and disease, striving for the development of microbiota-modulating therapeutics. Traditionally, germ-free mice have been the principal option for establishing human microbiota-associated (HMA) mouse models, leading to significant insights into the composition and function of the human microbiota. However, there are limitations in using germ-free mice as recipients of human microbiota, including considerable resource allocation to establish and maintain the model and incomplete development of their immune system and physiological functions. Thus, antibiotic-treated, non-germ-free mice have been developed as an alternative to satisfy the growing demand for an accessible HMA mouse model. Several methods have been described for creating "humanized" mice. These protocols vary in their key components, mainly antibiotic conditioning and frequency of oral gavage. To address this practical challenge and formulate a simple and repeatable protocol, we established a HMA mouse model with antibiotic-treated conventional and specific-pathogen free (SPF) C57BL/6J mice, revealing that a single oral gavage allows stable engraftment of the human microbiota. In this chapter, we present our simple protocol for antibiotic conditioning to prepare mice for stable engraftment of human gut microbiota.
移植了人类微生物群的小鼠是研究微生物群在健康和疾病中的作用、推动微生物群调节疗法发展的重要工具。传统上，无菌小鼠一直是建立人类微生物群相关（HMA）小鼠模型的主要选择，这为深入了解人类微生物群的组成和功能提供了重要见解。然而，将无菌小鼠用作人类微生物群的受体存在局限性，包括建立和维持该模型需要大量资源，以及其免疫系统和生理功能发育不完全。因此，已开发出经抗生素处理的非无菌小鼠作为替代方案，以满足对易于获得的HMA小鼠模型日益增长的需求。已经描述了几种创建“人源化”小鼠的方法。这些方案的关键组成部分各不相同，主要是抗生素预处理和灌胃频率。为应对这一实际挑战并制定一个简单且可重复的方案，我们用经抗生素处理的常规和无特定病原体（SPF）C57BL/6J小鼠建立了一个HMA小鼠模型，结果表明单次灌胃就能使人源微生物群稳定植入。在本章中，我们介绍了用于抗生素预处理的简单方案，以使小鼠能够稳定植入人类肠道微生物群。
